摘要:

A pharmacokinetic study is described in which Friesian calves (n = 30) were treated orally with clenbuterol at 10 times the therapeutic dose. The study was designed to establish the distribution and elimination of clenbuterol from edible tissues, the major compartments of the eye and body fluids. Animals (n= 24) were dosed (10 μg/kg body weight) twice daily with clenbuterol for 21 days and slaughtered in groups of five (one untreated control animal per group) at 6 h and 1, 2, 4, 8 and 16 days after cessation of treatment At slaughter, samples of diaphragm muscle, liver, kidney, bile, urine and both eyes were obtained. One of the eyes was separated into constituent tissues: aqueous humour, vitreous humour, comea, lens, retina (without pigmented epithelium), choroid (with pigmented retinal epithelium; choroid/PRE) and sclera. All samples were stored at ‐20°C. Clenbuterol concentrations were higher in liver than kidney, bile and urine from day 2 of withdrawal onwards. Concentrations in choroid/PRE were at least 10 times higher than in liver at all periods following cessation of treatment and 52 times higher 16 days after treatment The concentrations of clenbuterol in the constituent tissues of the eye were in the order choroid/PRE>comea>sclera>retina>aqueous humour/vitreous humour ≥ lens. Concentrations of clenbuterol in choroid/PRE taken from eyes frozen whole were generally lower than those in choroid/PRE separated before storage. Choroid/PRE stored by either method contained clenbuterol at more than 100 ng/g 16 days following cessation of treatment These data suggest that analysis of choroid taken at the abattoir would provide reliable surveillance information on the use or abuse of clenbuterol within the slaughter population. It is proposed that liver samples taken concurrently could be used in the event of a positive result from choroid/PRE analysis to indicate whether the maximum residue limit for edible tissues has been exc

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00559.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

A controlled study examining the effects of the cardioselective muscarinic cholinergic antagonist methoctramine on fentanyl‐induced bradycardia was performed in six dogs. Five doses of methoctramine (6, 10, 20, 30 and 60 |ig/kg) followed by fentanyl (20 μg/kg) were administered randomly on separate days. Fentanyl caused a significant reduction in heart rate from baseline values. Moreover, fentanyl produced a variety of arrhythmogenic actions indicative of vagal hyper‐activity, including sinus bradycardia, second‐degree atrioventricular block and ventricular and supraventricular escape beats. Administration of methoctramine 5 min before fentanyl injection prevented the bradycardic effects of fentanyl in a dose‐dependent manner, with high doses of methoctramine causing sinus tachycardia. Using regression analysis, the dose of methoctramine necessary to prevent fentanyl‐induced bradyarrhythmias without causing tachycardia was calculated as 14.4 μg/kg. The study confirmed that fentanyl administration in the conscious dog causes profound bradycardia with bradyarrhythmias. The cardioselective muscarinic antagonist agent methoctramine prevented the bradycardic effects

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00560.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Cefixime is a unique third‐generation oral cephalosporin. Itsin vitroactivity and pharmacokinetic properties have been studied to assess its potential for use in the therapy of newborn calf infections due to gram‐negative bacteria. The minimum inhibitory concentrations of cefixime for 90% (MIC50) of field isolates ofEscherichia coli. SalmonellaandPasteurellawere 0.10–0.40 μg/mL. The serum disposition kinetics of cefixime following intravenous and oral administration was evaluated. The elimination half‐life of cefixime after intravenous and oral administration was 3.5–4.0 h, the steady‐state volume of distribution was 0.34 L/kg and approximately 90% of the drug was bound to serum proteins. Oral absorption was comparatively slow and bioavailability values for single 5 mg/kg doses were 20.2% after the administration of 200 mg of cefixime in capsules, 28.3% after dosing an aqueous solution of cefixime and 35.7% after fasted calves received the solution of cefixime. Mean serum drug concentrations 12 h after the cefixime solution was administered orally (5 mg/kg) were 1.05 μg/mL for the milk‐fed calves and 1.76 μg/mL for the fasted calves. Computations showed that mean free drug concentrations equal to the MIC50of the drug for gram‐negative pathogens associated with newborn calf infections can be maintained in tissues by multiple treatments at 5 mg/kg every 12 h or 1

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00561.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

An aqueous solution of norfloxacin nicotinate (NFN) was administered to donkeys (Aquus astnus) intravenously (once at 10 mg/kg), intramuscularly and orally (both routes once at 10 and 20 mg/kg, and for 5 days at 20 mg/kg/day). Blood samples were collected at predetermined times after each treatment and urine was sampled after intravenous drug administration. Serum NFN concentrations were determined by microbiological assay. Intravenous injection of NFN over 45–60 s resulted in seizures, profuse sweating and tachycardia. The intravenous half‐life (t1/2βwas 209 ± 36 min, the apparent volume of distribution (Vd(area)) was 3.34 ± 0.58 L/kg, the total body clearance (ClE) was 1.092 ± 0.123 ± 10‐‐2mL/min/kg and the renal clearance (C1R) was 0.411 ± 0.057 ± 10‐‐2mL/min/kg. Oral bioavailability was rather poor (9.6% and 6.4% for the 10 and 20 mg/kg doses respectively). Multiple oral treatments did not result in any clinical gastrointestinal disturbances.After intramuscular administration (20 mg/kg), serum NFN concentrations>0.25 μg/mL (necessary to inhibit the majority of gram‐negative bacteria isolated from horses) were maintained for 12 h. The intramuscular bioavailability was 31.5% and 18.8% for the 10 and 20 mg/kg doses respectively. After multiple dosing some local swelling was observed at the injection site. About 40% of the intravenous dose was recovered in the urine as parent drug. The results of comprehensive haematological and blood biochemistry tests indicated no abnormal findings except elevation in serum CPK (creatine phosphokinase) values after multiple intramuscular dosing. On the basis of thein vitro‐determined minimum inhibitory concentrations of the drug and serum concentrations after multiple dosing, the suggested intramuscular dosage schedules for the treatment of gram‐negative bacterial infections in Equidae are 10 mg/kg every 12

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00562.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The pharmacokinetics and urinary excretion of ketoprofen in six healthy mares after the first and last of five daily intravenous doses of 2.2 mg of ketoprofen per kg body weight were investigated using a high‐performance liquid chromatographic (HPLC) method for determining plasma and urinary ketoprofen concentrations. Plasma ketoprofen concentrations declined triexponentially after each dose with no significant differences in plasma concentrations or pharmacokinetic parameter values between the first and last doses. The harmonic mean of the terminal elimination half‐life of ketoprofen after the first and last dose was 98.2 and 78.0 min, respectively. The median values of the total plasma clearance and the renal clearance after the first dose were 4.81 and 1.93 mL/min/kg, respectively. Total plasma clearance was attributed to renal excretion of ketoprofen and metabolism of ketoprofen to a base‐labile conjugate which was also excreted in the urine. Renal clearance of ketoprofen was attributed to renal tubular secretion since renal clearance was greater than filtration clearance. Urinary recovery of ketoprofen during the first 420 min after the first dose accounted for 26.4% of the dose as unconjugated ketoprofen and 29.8% of the dose as a base‐labile conjugate of ketoprofen. Total urinary recovery of ketoprofen as unchanged ketoprofen and from base‐labile conjugate represented 56.2% of the dose. Plasma protein binding of ketoprofen was extensive; the mean plasma protein binding of ketoprofen was 92.8% (SD 3.0%) at 500 ng/mL and 91.6% (SD 0.60%) at 1

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00563.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The disposition of intravenously (0.5 mg/kg) and orally (5 mg/kg) administered verapamil was studied in six dogs after 3 days' pre‐treatment with verapamil alone (5 mg/kg, every 8 h) and during concomitant oral administration of cimetidine (16 mg/kg, every 8 h). Racemic verapamil and norverapamil, an active metabolite of verapamil, were measured by fluorescence high performance liquid chromatography using an achiral phenyl column. The isolated racemic verapamil was rechromatographed on an Ultron‐OVM chiral column, which separated the two verapamil enantiomers. Cimetidine co‐administration significantly reduced the systemic clearance of racemic verapamil as well as that of its enantiomers by 25–29%. The clearance of racemic verapamil administered orally as well as that of its enantiomers was also reduced by 28% during cimetidine coadministration. The decrease in verapamil metabolism by cimetidine appeared to be non‐stereoselective. On the other hand, cimetidine co‐administration had no significant effect on the apparent volume of distribution of racemic verapamil and its enantiomers or the plasma protein binding or the blood to plasma concentration ratio of racemic verapamil. In addition, the ratio of the area under the plasma concentration‐time curve for norverapamil to that of verapamil was unaffected by cimetidine co‐administration. These results suggest that cimetidine alters the disposition of verapamil by decreasing the hepatic blood flow rate and by inhibition of its first

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00564.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Plasma (P), synovial fluid (SF) and lymph (L) concentrations of gentamicin were studied in two trials. A lymph vessel in the hindlimb was cannulated. The day after surgery (trial A), P and L samples were collected for 12 h after intravenous injection of gentamicin sulphate at 2.2 mg/kg dose rate. Approximately 48 h after surgery (trial B), the fetlock joint of the cannulated hindlimb was catheterized and P, SF and L samples collected for 12 h after a similar intravenous injection. The kinetic parameters were similar to those in other reports and did not differ between trials (P<0.05). The P, L and SF disposition profiles were similar. The 95% confidence interval for P&L concentrations overlapped 2–3 h after injection. Thereafter, parallelism between L and P concentrations was observed, but L concentrations were on average 60% higher than P concentrations, and elimination from L was slower than from P. The mean L/SF and P/SF ratios were 1.54 ± 0.2 and 1.25 ± 0.2, 2–4 h after injection. Gentamicin elimination from SF appeared to be slower than from L and P. Lymph cannulation is a viable technique for antibiotic disposition studies. A sample of any of the fluids 3 h after injection was representative of the others. While SF concentrations were of limited value for predicting tissue fluid (L) concentrations 3–8 after injection, P concentrations were a usefu

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00565.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The pharmacokinetic behaviour of an amoxicillin/clavulanic acid combination was studied after intravenous administration of single doses (20 mg/kg per kg body weight) to five sheep and six goats. The objective was to determine whether there are differences between sheep and goats in the disposition of amoxicillin and clavulanic acid. The plasma concentration‐time data were analysed by compartmental pharmacokinetic and non‐compartmental methods. The disposition curves for both drugs were best described by a biexponential equation (two‐compartment open model) in sheep and goats. The elimination half‐lives of amoxicillin were 1.43 ± 0.16 h in sheep and 1.13 ± 0.19 h in goats, and of clavulanic acid were 1.16 ± 0.01 h and 0.85 ± 0.09 h in sheep and goats respectively. The apparent volumes of distribution of amoxicillin and clavulanic acid were similar in the two species. Body clearances of amoxicillin were 0.09 ± 0.01 L/h kg in sheep and 0.11 ± 0.01 L/h kg in goats, and of clavulanic acid were 0.07 ± 0.01 L/h kg and 0.12 ± 0.01 L/h kg in sheep and goats respectively. The half‐lives and body clearances of amoxicillin and clavulanic acid differed significantly between sheep and goats. It was concluded that the disposition of amoxicillin and clavulanic acid administered intravenously as an amoxicillin/clavulanic acid combination to sheep and goats differed between the two ruminant species. Even though the differences in disposition kinetics of both drugs were statistically significant, the same intravenous dosing rate of this antimicrobial combination can generally be used i

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00566.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

In the present study the effects of water deprivation in the camel (Camelus dromedarius) on the pharmacokinetic profile of antipyrine were assessed. A crossover design was used. The pharmacokinetics of antipyrine in adult and young camels were compared. Antipyrine was administered intravenously to young and adult female camels when water was availablead libitumand to the adult camels after 14 days of dehydration. The elimination half‐life of antipyrine in watered adult camels was 136.5 ± 16.7 min. The half‐life of elimination and the mean residence time of antipyrine were significantly prolonged following dehydration. The observed effects of water deprivation were not a function of age, as the pharmacokinetic profile of antipyrine in young camels was similar to that of the adults, but more likely due to the changes in oxidative metabolic capacity of the liver as a result of a reduced general metabolism. The results of the present study also show that the intrinsic clearance of antipyrine is proportional to the camel's body weight, as previously shown for other mammalian spe

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00567.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The effect of human recombinant insulin‐like growth factor 1 (rhIGF‐1) on proteoglycan (PG) metabolism of full thickness equine articular cartilage explants was investigated. PG synthesis was stimulated at all ages, but higher concentrations of rhIGF‐1 were required for maximal stimulation of adult cartilage. There were no changes in the hydrodynamic size, electrophoretic heterogeneity or composition of proteoglycans isolated from rhIGF‐1‐stimulated cartilage. rhIGF‐1 reduced the rate of turnover of both newly synthesized and endogenous proteoglycans in all ages of cartilage investigated. The structure of proteoglycan fragments retained within the matrix and those released into the culture medium was unaffected by IGF‐1 stimulation, suggesting that this peptide is a key regulator of the proteoglycan composition of equine articular cartilage extrace

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00568.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY